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Animal ionotropic glutamate receptors (iGLRs) and members of subfamily C (Kolakowski 1994) or IV (Parmentier et al. 1998) of the G-protein-coupled receptors (subC-GPCRs), which contains the metabotropic glutamate receptors (mGLRs) and g-aminobutyric acidB receptors (GABA-BRs), have distinct pharmacological and structural characteristics (Sutcliffe, Wo, and Oswald 1996; Walker, Brooks, and Holden-Dye 1996; Sutcliffe et al. 1998). Likeness among members of the two superfamilies has been noted in the literature. The iGLRs share sequence similarity with regions of the mGLRs (Walker, Brooks, and Holden-Dye 1996), and mGLRs share sequence similarity with GABA-BRs (Kaupmann et al. 1997). In addition, all of the receptors, iGLRs (Wo and Oswald 1995), mGLRs (O’Hara et al. 1993), and GABA-BRs (Galvez et al. 1999), have sequence similarities to portions of the bacterial periplasmic binding proteins. An evolutionary link between the iGLRs and the periplasmic binding proteins has been demonstrated (Chiu et al. 1999) via a newly identified family of genes encoding for putative GLRs in plants (Lam et al. 1998). Despite the noted similarities among the iGLRs and members of subC-GPCRs, namely, the mGLRS or GABA-BRs, there are no data to support an evolutionary link between any member of the two superfamilies, including one between members of the mGLRs and iGLRs (Walker, Brooks, and Holden-Dye 1996). We provide evidence for a link between the iGLRs and members of subC-GPCRs by incongruence length difference, parsimony, and bootstrap analyses. We demonstrate that the N-terminal regions of the putative GLRs from plants are related to members of subCGPCRs and that the C-terminal regions of the putative GLRs from plants are related to iGLRs. From this discordant relationship, we conclude that the ancestors of the plant GLRs may be the evolutionary progenitors of members of both superfamilies of highly specialized animal receptors via distinct evolutionary mechanisms. A

molecular biology and evolution

The Putative Glutamate Receptors from Plants Are Related to Two Superfamilies of Animal Neurotransmitter Receptors via Distinct Evolutionary Mechanisms